Mechanisms involved in hydrocarbon-induced malignant transformation will be studied in an in vitro model system for chemical carcinogenesis which employs fibroblasts from mouse prostate. Our studies on the metabolic activation of polycyclic aromatic hydrocarbons will be continued; especially the biologic activity of diol-epoxides will be investigated. Recent findings suggest such derivatives to be ultimate carcinogens in the case of some, if not all, hydrocarbons. Our studies on the binding of hydrocarbons and their derivatives to DNA and on the capacity of these compounds to induce DNA repair will be continued. Our studies led us to suggest that reverse transcriptase may play a role in chemical transformation, too: we will continue to study the effect of inhibitors of this enzyme activity on chemically induced transformation and to investigate whether the activity of this enzyme changes during the course of transformation-induction. Moreover, we will further explore the suitability of our in vitro model system to predict the oncogenic potential of environmental chemicals. For instance, in such an effort we had seen that the radical-scavenger, cysteamine, inhibits tumorigenesis in vivo and malignant transformation in vitro induced by chemicals, and we had observed a good correlation between in vivo tumorigenesis and in vitro oncogenesis with the anthracycline antitumor antibiotics, adriamycin and daunomycin. BIBLIOGRAPHIC REFERENCES: Philips, F.S., Gilladoga, A., Marquardt, H., and Sternberg, S.S. Some observations on the toxicity of adriamycin. Cancer Chemotherapy Reports, Part 3, 6: 177-181, 1975. Marquardt, H. Reserpine and Chemical Carcinogenesis. The Lancet, I (1975), 925-926.